(3) The COMT genotype is related to performance on prefrontal cortex-dependent tasks and may contribute to the deficit in prefrontal-dependent memory processes in SPD as it does in schizophrenia.
Catechol O-methyltransferase Val158Met polymorphism in schizophrenia: differential effects of Val and Met alleles on cognitive stability and flexibility.
An attractive candidate gene for schizophrenia is the catechol-O-methyltransferase (COMT) gene, which is a modulator of dorsolateral prefrontal cortical function.
Findings suggest that anhedonia is manifest in individuals who carry genetic liability for schizophrenia and is associated with the Val(158)Met polymorphism of the COMT gene.
Similar to our previously reported findings, a statistically significant association was found between aggressive behavior in SZ and the COMT 158 polymorphism; mean LHA scores were higher in subjects homozygous for 158Met, the low enzyme activity COMT variant (F(2,105) = 5.616, P = 0.005).
The COMT Val allele is associated with an increased risk of schizophrenia in subjects at increased familial risk, in whom it has demonstrable effects on prefrontal brain structure and function.
The authors tested for an association between a COMT haplotype and schizophrenia-spectrum disorders and for an eventual influence of a specific COMT genotype in the clinical outcome and in the response to treatment.
The C957T polymorphism in the dopamine D2 receptor (DRD2) gene and the Val158Met polymorphism in the Catechol-O-Methyl-Transferase (COMT) gene affect dopamine transmission and have been found to be associated with schizophrenia.
The disease-related laminar difference of COMT expression may be involved in dysregulation of dopamine signaling circuits in the DLPFC of patients with schizophrenia.
The present work examines evidence for the role of COMT in schizophrenia pathogenesis, and associations between COMT and cognitive and behavioral correlates of schizophrenia and related disorders.
The subset of relatives of schizophrenia patients who were COMT val homozygotes exhibited lower scores on narcissism, rejectionality, and stimulus seeking than met homozygote relatives of schizophrenia patients and control participants.
These findings are consistent with epistatic effects of the COMT and MTHFR polymorphisms on prefrontal dopamine signaling, and suggest that in schizophrenia patients, the MTHFR 677T allele exacerbates prefrontal dopamine deficiency.